1. Field of Invention
In some embodiments, the present invention generally relates to a drug-free biodegradable 3-dimentioned porous collagen-glycosaminoglycan scaffold serving as an implantation device, and in particular to a device designed for preventing scar formation and creating a physiological aqua buffer environment in conjunctival space for modulating the intraocular pressure on glaucoma.
2. Background
Glaucoma encompasses serial symptoms such as intraocular pressure elevation, optic nerve damage and progressive visual field loss. Most patients receive medical treatments by oral ingestion or locally applying beta-blockers, miotics, adrenergic agonists or carbonic anhydrase inhibitors to enhance water reabsorption by blood vessels and consequently lower the intraocular pressure. Most of the patients significantly respond to drug therapy at the beginning, but in many cases turn out to be refractory over time. For the individual who fails to quickly respond to drug treatment, surgical intervention is required in order to maintain intraocular pressure.
Glaucoma filtering surgery is the current operating process for reducing intraocular pressure. The processes of glaucoma filtering surgery consists of making an opening through the trabeculum to drain out aqueous humor from the anterior chamber, and building a filtering bleb or drainage fistula between the anterior chamber and the subconjunctival space to reduce intraocular pressure (Bergstrom et al., 1991; Miller et al., 1989). However, the scar development after surgery results in the obstruction of the built filtering bleb or drainage fistula and finally leads to the recurrence of high intraocular pressure (Peiffer et al., 1989). Hence, the prevention of scar formation should be an important consideration for the success of glaucoma surgery.
Clinical treatments use mitomycin-C, 5-fluorouracil, bleomycin, beta-aminopropionitrile, D-penicillamine, tissue plasminogen activator and corticosteroid for the inhibition of fibroblast proliferation to prevent scar development after glaucoma surgery. Nevertheless, observed side effects, such as thinning of the conjunctiva or intraocular inflammation can lead to blindness.
U.S. Pat. No. 5,713,844 and U.S. Pat. No. 5,743,868 disclosed pump- or tube-like devices made with artificial materials being implanted into the subconjunctival space or the anterior chamber surroundings as an alternative to the filtering bleb or drainage fistula to lower the intraocular pressure. These non-degradable devices function as the fistula and bleb, giving short-term benefits but the procedure eventually fails due to scar formation. Moreover, the devices are not biodegradable, causing incommodity and risk of secondary infection. In addition, no clinical observation shows significant reduction of scar formation after implanting such devices. As a matter of fact, the regenerative tissue often invades or pinches into the implanted devices, consequently obstructing the outflow pathway. For the most part, it is not a general therapeutic consideration.
For years, studies on tissue engineering achieved great progress in scar prevention (Yannas et al., 1989; Yannas, 1998). For example, artificial skin contributes great benefits to wound healing (Orgill et al., 1996; Yannas et al., 1982). U.S. Pat. No. 4,060,081 and U.S. Pat. No. 5,489,304 disclosed artificial skin to benefit wound healing and prevent scar formation. Both types of artificial skin combine a degradable layer and another non-degradable layer. The non-degradable layer composed of synthetic polymers controls moisture flux of the skin; and the degradable layer composed of a three-dimensioned (3D) collagen-mucopolysaccharide or collagen-glycosaminoglycan copolymer directly covers the wound area to support tissue regeneration. The 3D collagen-mucopolysaccharide or collagen-glycosaminoglycan copolymers lead a random reorganization of the regenerating fibroblasts and the secreted intercellular matrix, and finally result in a reduction of scar formation.
To mimic skin physiological function, some of the prior methods and devices have been designed with a high intensity of chemical linkage between components and functional control of the moisture flux. In addition, these products are generally for external application, rather than for use as an implanting device. It is not possible to apply such artificial skin as an implanting device directly in a glaucoma treatment. Another resolution for preventing scar formation and modulating intraocular pressure after glaucoma surgery is highly desirable.
U.S. Pat. No. 6,299,895 and U.S. Pat. No. 6,063,116 disclosed implanting devices, which carried different biological active molecules to inhibit cell proliferation, amend tissue regeneration and prevent scar development. However, the building components are not fully biodegradable. U.S. Pat. No. 6,013,628 and U.S. Pat. No. 6,218,360 presented a combination of cell proliferating inhibitors and different biodegradable mediators, and the direct application into the intraocular tissue. Although these patents addressed the problem of the non-degradability of the drug mediator, there is still the risk that the drug may leak out from the injecting site. The affected area will be beyond control. Moreover, such a biodegradable matrix does not function as a pressure regulator capable of modulating the intraocular pressure through a physical means, i.e., to modulate the pressure of the intraocular fluid by establishing a physiological aqua buffer reservoir.